RT bij hersenmetastasen
Radiotherapy as a treatment option for brain metastases
A. M. Méndez Romero en P. J. C. M. Nowak
Afdeling radiotherapie, Erasmus MC
18 januari 2010
Brain metastases are the most common intracranial neoplasm in adults, and they represent an important cause of cancer morbidity and mortality for cancer patients. The majority of brain metastases originate from one of three primary malignancies: lung cancer, breast cancer, and melanoma. Therapeutic approaches to brain metastases include surgery, stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and chemotherapy. Appropriate management of patients with brain metastases requires an assessment of independent prognostic factors in order to maximize survival and neurological function while avoiding unnecessary treatments.
Demographic and clinical variables predictive of survival have been studied. A validated prognostic category index was derived from the Radiation Therapy Oncology Group (RTOG) database using recursive-partitioning analysis (RPA) (1). RPA class 1 with a median survival of 7.1 months, is defined as those with Karnofsky score ³70%, age <65 years, controlled primary tumor with the brain as the only site of metastases. RPA class 3 with a median survival of 2.3 months, is defined as those with Karnofsky score <70%. All other patients had relatively minor differences in survival, 4.2 months, and were included in the RPA class 2. Although the distinction of single versus multiple brain metastases did not retain significance in the original RPA model, it may hold additional prognostic value within classes 1 and 2.
RPA classes 1-2 and single brain metastases
Randomized trials have demonstrated that the combination of surgery and WBRT is superior to WBRT alone for the treatment of patients with single brain metastases and limited or absent systemic disease and good condition (2,3). Surgical resection should be considered in patients with a metastasis in an accessible location, especially when the size is large, the mass effect is considerable or an obstructive hydrocephalus is present.
A randomized trial has evidenced that survival and freedom from local recurrence were not significantly different between SRS alone vs. surgery combined with WBRT (4). Distant brain recurrences were more often experienced in the SRS group. Another randomized trial between WBRT vs. SRS and WBRT has observed a survival advantage in the SRS and WBRT group. SRS should be considered in those patients with good condition, relatively controlled systemic disease or with available systemic treatment options, and with metastases diameter ≤4cm, especially when located in eloquent regions (5).
RPA classes 1-2 and multiple brain metastases
RPA classes 1-2 and multiple brain metastases
For patients with up to three or four brain metastases, diameter ≤3-4cm, good condition, and relatively controlled systemic disease or with available systemic treatment options, SRS is a better alternative to WBRT regarding local control, although no survival benefit has been demonstrated above WBRT alone in two randomized trials (5,6).
It is still controversial whether adjuvant WBRT, whose rationale is destroying microscopic metastatic deposits at original tumor site or at distant intracranial locations, is necessary after SRS. One randomized study demonstrated no survival benefit of SRS combined with WBRT vs. SRS alone, although brain tumor recurrence was higher for the SRS alone group (7). Salvage treatment was more required in the SRS group. Death attributed to neurological causes was not different for both groups. Results from large randomized trials about the role of WBRT in addition to SRS (EORTC 22952-26001, Z0300 American College Association of Surgeons) are necessary to evaluate the impact of brain recurrences on patients’ neurological function and quality of life.
RPA class 3
RPA class 3
For patients with a Karnofsky score < 70%, WBRT might be considered, if patients are not bedridden. Different irradiation schedules have been evaluated in several trials by the RTOG to determine palliative effectiveness in patients with metastatic brain disease (8). The results of these studies showed that shorter time-dose fractionation schemes such as 30 Gy in 2 weeks or 20 Gy in 1 week might be used with equal efficacy.
REFERENCES
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6. Kondziolka D, Patel A, Lunsford LD, et al. Stereotactic radiosurgery plus whole brain radiotherapy versus radiotherapy alone for patients with multiple brain metastases. Int J Radiat Oncol Biol Phys 1999; 45(2):427-434.
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8. Borgelt B, Gelber R, Kramer S, et al. The palliation of brain metastases: final results of the first two studies by the Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 1980; 6(1):1-9.
Laatste Wijziging: 03-02-2010